Title : GWAS meta-analysis of over 29,000 people with epilepsy identifies 26 risk loci and subtype-specific genetic architecture Language : English Author, co-author : Stevelink, Remi [> >] Campbell, Ciarán [> >] Chen, Siwei [> >] Abou-Khalil, Bassel [> >] Adesoji, Oluyomi M. [> >] Afawi, Zaid [> >] Amadori, Elisabetta [> >] Anderson, Alison [> >] Anderson, Joseph [> >] Andrade, Danielle M. [> >] Annesi, Grazia [> >] Auce, Pauls [> >] Avbersek, Andreja [> >] Bahlo, Melanie [> >] Baker, Mark D. [> >] Balagura, Ganna [> >] Balestrini, Simona [> >] Barba, Carmen [> >] Barboza, Karen [> >] Bartolomei, Fabrice [> >] Bast, Thomas [> >] Baum, Larry [> >] Baumgartner, Tobias [> >] Baykan, Betül [> >] Bebek, Nerses [> >] Becker, Albert J. [> >] Becker, Felicitas [> >] Bennett, Caitlin A. [> >] Berghuis, Bianca [> >] Berkovic, Samuel F. [> >] Beydoun, Ahmad [> >] Bianchini, Claudia [> >] Bisulli, Francesca [> >] Blatt, Ilan [> >] Bobbili, Dheeraj Reddy [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] Borggraefe, Ingo [> >] Bosselmann, Christian [> >] Braatz, Vera [> >] Bradfield, Jonathan P. [> >] Brockmann, Knut [> >] Brody, Lawrence C. [> >] Buono, Russell J. [> >] Busch, Robyn M. [> >] Caglayan, Hande [> >] Campbell, Ellen [> >] Canafoglia, Laura [> >] Canavati, Christina [> >] Cascino, Gregory D. [> >] Castellotti, Barbara [> >] Catarino, Claudia B. [> >] Cavalleri, Gianpiero L. [> >] Cerrato, Felecia [> >] Chassoux, Francine [> >] Cherny, Stacey S. [> >] Cheung, Ching-Lung [> >] Chinthapalli, Krishna [> >] Chou, I.-Jun [> >] Chung, Seo-Kyung [> >] Churchhouse, Claire [> >] Clark, Peggy O. [> >] Cole, Andrew J. [> >] Compston, Alastair [> >] Coppola, Antonietta [> >] Cosico, Mahgenn [> >] Cossette, Patrick [> >] Craig, John J. [> >] Cusick, Caroline [> >] Daly, Mark J. [> >] Davis, Lea K. [> >] de Haan, Gerrit-Jan [> >] Delanty, Norman [> >] Depondt, Chantal [> >] Derambure, Philippe [> >] Devinsky, Orrin [> >] Di Vito, Lidia [> >] Dlugos, Dennis J. [> >] Doccini, Viola [> >] Doherty, Colin P. [> >] El-Naggar, Hany [> >] Elger, Christian E. [> >] Ellis, Colin A. [> >] Eriksson, Johan G. [> >] Faucon, Annika [> >] Feng, Yen-Chen A. [> >] Ferguson, Lisa [> >] Ferraro, Thomas N. [> >] Ferri, Lorenzo [> >] Feucht, Martha [> >] Fitzgerald, Mark [> >] Fonferko-Shadrach, Beata [> >] Fortunato, Francesco [> >] Franceschetti, Silvana [> >] Franke, Andre [> >] French, Jacqueline A. [> >] Freri, Elena [> >] Gagliardi, Monica [> >] Gambardella, Antonio [> >] Geller, Eric B. [> >] Giangregorio, Tania [> >] Gjerstad, Leif [> >] Glauser, Tracy [> >] Goldberg, Ethan [> >] Goldman, Alicia [> >] Granata, Tiziana [> >] Greenberg, David A. [> >] Guerrini, Renzo [> >] Gupta, Namrata [> >] Haas, Kevin F. [> >] Hakonarson, Hakon [> >] Hallmann, Kerstin [> >] Hassanin, Emadeldin Saeed Fathy Sayed [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] Hegde, Manu [> >] Heinzen, Erin L. [> >] Helbig, Ingo [> >] Hengsbach, Christian [> >] Heyne, Henrike O. [> >] Hirose, Shinichi [> >] Hirsch, Edouard [> >] Hjalgrim, Helle [> >] Howrigan, Daniel P. [> >] Hucks, Donald [> >] Hung, Po-Cheng [> >] Iacomino, Michele [> >] Imbach, Lukas L. [> >] Inoue, Yushi [> >] Ishii, Atsushi [> >] Jamnadas-Khoda, Jennifer [> >] Jehi, Lara [> >] Johnson, Michael R. [> >] Kälviäinen, Reetta [> >] Kamatani, Yoichiro [> >] Kanaan, Moien [> >] Kanai, Masahiro [> >] Kantanen, Anne-Mari [> >] Kara, Bülent [> >] Kariuki, Symon M. [> >] Kasperavičiūte, Dalia [> >] Kasteleijn-Nolst Trenite, Dorothee [> >] Kato, Mitsuhiro [> >] Kegele, Josua [> >] Kesim, Yeşim [> >] Khoueiry-Zgheib, Nathalie [> >] King, Chontelle [> >] Kirsch, Heidi E. [> >] Klein, Karl M. [> >] Kluger, Gerhard [> >] Knake, Susanne [> >] Knowlton, Robert C. [> >] Koeleman, Bobby P. C. [> >] Korczyn, Amos D. [> >] Koupparis, Andreas [> >] Kousiappa, Ioanna [> >] Krause, Roland [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] Krenn, Martin [> >] Krestel, Heinz [> >] Krey, Ilona [> >] Kunz, Wolfram S. [> >] Kurki, Mitja I. [> >] Kurlemann, Gerhard [> >] Kuzniecky, Ruben [> >] Kwan, Patrick [> >] Labate, Angelo [> >] Lacey, Austin [> >] Lal, Dennis [> >] Landoulsi, Zied [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] Lau, Yu-Lung [> >] Lauxmann, Stephen [> >] Leech, Stephanie L. [> >] Lehesjoki, Anna-Elina [> >] Lemke, Johannes R. [> >] Lerche, Holger [> >] Lesca, Gaetan [> >] Leu, Costin [> >] Lewin, Naomi [> >] Lewis-Smith, David [> >] Li, Gloria H.-Y. [> >] Li, Qingqin S. [> >] Licchetta, Laura [> >] Lin, Kuang-Lin [> >] Lindhout, Dick [> >] Linnankivi, Tarja [> >] Lopes-Cendes, Iscia [> >] Lowenstein, Daniel H. [> >] Lui, Colin H. T. [> >] Madia, Francesca [> >] Magnusson, Sigurdur [> >] Marson, Anthony G. [> >] May, Patrick [University of Luxembourg > Luxembourg Centre for Systems Biomedicine (LCSB) > Bioinformatics Core] McGraw, Christopher M. [> >] Mei, Davide [> >] Mills, James L. [> >] Minardi, Raffaella [> >] Mirza, Nasir [> >] Møller, Rikke S. [> >] Molloy, Anne M. [> >] Montomoli, Martino [> >] Mostacci, Barbara [> >] Muccioli, Lorenzo [> >] Muhle, Hiltrud [> >] Müller-Schlüter, Karen [> >] Najm, Imad M. [> >] Nasreddine, Wassim [> >] Neale, Benjamin M. [> >] Neubauer, Bernd [> >] Newton, Charles R. J. C. [> >] Nöthen, Markus M. [> >] Nothnagel, Michael [> >] Nürnberg, Peter [> >] O’Brien, Terence J. [> >] Okada, Yukinori [> >] Ólafsson, Elías [> >] Oliver, Karen L. [> >] Özkara, Çiğdem [> >] Palotie, Aarno [> >] Pangilinan, Faith [> >] Papacostas, Savvas S. [> >] Parrini, Elena [> >] Pato, Carlos N. [> >] Pato, Michele T. [> >] Pendziwiat, Manuela [> >] Petrovski, Slavé [> >] Pickrell, William O. [> >] Pinsky, Rebecca [> >] Pippucci, Tommaso [> >] Poduri, Annapurna [> >] Pondrelli, Federica [> >] Powell, Rob H. W. [> >] Privitera, Michael [> >] Rademacher, Annika [> >] Radtke, Rodney [> >] Ragona, Francesca [> >] Rau, Sarah [> >] Rees, Mark I. [> >] Regan, Brigid M. [> >] Reif, Philipp S. [> >] Rhelms, Sylvain [> >] Riva, Antonella [> >] Rosenow, Felix [> >] Ryvlin, Philippe [> >] Saarela, Anni [> >] Sadleir, Lynette G. [> >] Sander, Josemir W. [> >] Sander, Thomas [> >] Scala, Marcello [> >] Scattergood, Theresa [> >] Schachter, Steven C. [> >] Schankin, Christoph J. [> >] Scheffer, Ingrid E. [> >] Schmitz, Bettina [> >] Schoch, Susanne [> >] Schubert-Bast, Susanne [> >] Schulze-Bonhage, Andreas [> >] Scudieri, Paolo [> >] Sham, Pak [> >] Sheidley, Beth R. [> >] Shih, Jerry J. [> >] Sills, Graeme J. [> >] Sisodiya, Sanjay M. [> >] Smith, Michael C. [> >] Smith, Philip E. [> >] Sonsma, Anja C. M. [> >] Speed, Doug [> >] Sperling, Michael R. [> >] Stefansson, Hreinn [> >] Stefansson, Kári [> >] Steinhoff, Bernhard J. [> >] Stephani, Ulrich [> >] Stewart, William C. [> >] Stipa, Carlotta [> >] Striano, Pasquale [> >] Stroink, Hans [> >] Strzelczyk, Adam [> >] Surges, Rainer [> >] Suzuki, Toshimitsu [> >] Tan, K. Meng [> >] Taneja, R. S. [> >] Tanteles, George A. [> >] Taubøll, Erik [> >] Thio, Liu Lin [> >] Thomas, G. Neil [> >] Thomas, Rhys H. [> >] Timonen, Oskari [> >] Tinuper, Paolo [> >] Todaro, Marian [> >] Topaloğlu, Pınar [> >] Tozzi, Rossana [> >] Tsai, Meng-Han [> >] Tumiene, Birute [> >] Turkdogan, Dilsad [> >] Unnsteinsdóttir, Unnur [> >] Utkus, Algirdas [> >] Vaidiswaran, Priya [> >] Valton, Luc [> >] van Baalen, Andreas [> >] Vetro, Annalisa [> >] Vining, Eileen P. G. [> >] Visscher, Frank [> >] von Brauchitsch, Sophie [> >] von Wrede, Randi [> >] Epilepsies, International League Against Epilepsy Consortium On Complex [> >] Publication date : 31-Jul-2023 Journal title : Nature Genetics Publisher : Nature Publishing Group Peer reviewed : Yes Audience : International ISSN : 1061-4036 e-ISSN : 1546-1718 City : New York Country : United Kingdom Keywords : [en] Epilepsy ; GWAS ; sub-phenotypesAbstract : [en] Epilepsy is a highly heritable disorder affecting over 50 million people worldwide, of which about one-third are resistant to current treatments. Here we report a multi-ancestry genome-wide association study including 29,944 cases, stratified into three broad categories and seven subtypes of epilepsy, and 52,538 controls. We identify 26 genome-wide significant loci, 19 of which are specific to genetic generalized epilepsy (GGE). We implicate 29 likely causal genes underlying these 26 loci. SNP-based heritability analyses show that common variants explain between 39.6 and 90 of genetic risk for GGE and its subtypes. Subtype analysis revealed markedly different genetic architectures between focal and generalized epilepsies. Gene-set analyses of GGE signals implicate synaptic processes in both excitatory and inhibitory neurons in the brain. Prioritized candidate genes overlap with monogenic epilepsy genes and with targets of current antiseizure medications. Finally, we leverage our results to identify alternate drugs with predicted efficacy if repurposed for epilepsy treatment.Research centres : Luxembourg Centre for Systems Biomedicine (LCSB): Bioinformatics Core (R. Schneider Group) Funders : Fonds National de la Recherche - FnR ; BMBF Target : Researchers ; Professionals ; Students Permalink : http://hdl.handle.net/10993/56044 DOI : 10.1038/s41588-023-01485-w Other URL : https://doi.org/10.1038/s41588-023-01485-w FnR project : FnR ; FNR16394868 > Alexander Skupin > MechEpi-2 > Epileptogenesis Of Genetic Epilepsies > 01/10/2021 > > 2021 
